This application is to establish the UNC-Malawi Cancer Consortium (UNC-MCC), to develop capacity and conduct high-impact research focused on HIV-associated cancers. The consortium builds on longstanding collaborations between the University of North Carolina at Chapel Hill (UNC-CH), Lighthouse Trust, Malawi Ministry of Health (MOH), and University of Malawi College of Medicine (COM). These partnerships have resulted in internationally recognized contributions for HIV care and prevention in sub-Saharan Africa. This infrastructure can now be leveraged for HIV-associated malignancies. UNC-MCC is focused on the herpesvirus-associated cancers, Kaposi sarcoma (KS), and lymphoma. Our consortium will be led by three principal investigators with highly complementary expertise (Satish Gopal MD, clinical research; Sam Phiri PhD, implementation science; Blossom Damania PhD, virology). The third research project undertaken by UNC-MCC attempts to develop risk-adapted, response-guided treatment concepts for HIV-associated lymphoma in Malawi. The project is led by three co-PIs, Drs. Satish Gopal (UNC Project-Malawi), Yohannie MIombe (COM), and Richard Nyasosela (MOH). Lymphoma is the most curable cancer among HIV-infected individuals in Malawi, and this project addresses the central problem that many patients likely receive more chemotherapy than is needed to cure them. This increases treatment-related complications in a setting where supportive care is limited, and compromises long-term survival. An ability to beti:er identify patients who are curable with less chemotherapy can optimize the balance between efficacy and toxicity. We will attempt to develop more risk-adapted and response-guided approaches to lymphoma treatment through the following aims: (1) to identify clinical variables and peripheral blood biomarkers associated with rapid achievement of durable clinical remission among HIV-associated lymphoma patients in Malawi; and (2) to identify tumor characteristics, including gene expression profiles, which are also associated with rapid achievement of durable clinical remission. These aims will build on existing work in Lilongwe as part of the NIH-funded KCH Lymphoma Study, enhanced by collaborators from the UNC-CH Vironomics Core and sequencing infrastructure developed to support UNC-CH participation in The Cancer Genome Atlas (TCGA) project. Leveraging these ample resources, the proposed research will yield insights which are informative to care of HIV-associated lymphoma throughout sub-Saharan Africa.